“Oxidative stress” is defined as a state where a living body has oxidative tendency as a result of an imbalance between production of reactive oxygen species (ROS) and antioxidative defense mechanisms in a living body. That is, excessive production of the ROS or a decrease in antioxidative ability leads to the oxidative stress.
The ROS oxidizes a lipid, in particular, a low-density lipoprotein (LDL) of a phopholipid to form a lipid peroxide and oxidized LDL, and oxidatively denatures and deactivates a protein to cause an oxidative damage of DNA. It is therefore said that the oxidative stress is involved in development of many diseases such as arteriosclerosis, cancer, various lifestyle-related diseases, Alzheimer's disease, and Parkinson's disease and promotes aging, through damages of cells and tissues and impairment of vital functions (for example, see Non Patent Document 1).
Further, the skin is in a state in which the ROS is easily produced by an irritation of an environmental factor such as an ultraviolet ray. The ROS in the skin causes, for example, destruction of a body tissue such as collagen to damage cells, resulting in skin symptoms such as wrinkles, a decrease in elasticity, an inflammation, and pigmentation. Also, the ROS is known to oxidize proteins and lipids in the scalp to cause hair loss (for example, Patent Documents 1 and 2).
Meanwhile, if the concentration of the lipid peroxide increases in blood, the lipid peroxide itself or an oxidative decomposition product thereof is known to act directly on nucleic acids and proteins to cause angiopathy, hepatic dysfunction, cataract, or the like. Moreover, the lipid peroxide causes injury of vascular endothelial cells, enhancement of platelet aggregation, formation of foam cells, or the like, and hence is considered to be a cause of arteriosclerosis.
For example, it is known that a primary lesion of arteriosclerosis is caused by an oxidized low-density lipoprotein (LDL), and that the easiest method of detecting oxidation of LDL is measurement of lipid peroxide (for example, Non Patent Document 2).
As antioxidants from natural products, vitamin E, vitamin C, a neutral fraction of an extract of a Helichrysum plant (for example, Patent Document 1), an extract of Chimaphila umbellata (for example, Patent Document 2), and the like are known.
In particular, known drugs or the like for inhibiting formation of a lipid peroxide in a living body include an agent containing sesamin and/or episesamin as an active ingredient (for example, Patent Document 3), an agent characterized by containing fructo-oligosaccharide (for example, Patent Document 4), an agent containing, as an active ingredient, an extract obtained by extraction from leaves of Psidium guajava L. (for example, Patent Document 5), an agent for inhibiting formation of a lipid peroxide characterized by containing an extract of a plant native to Mexico with a scientific name of Gnaphalium semiamlexicaule (for example, Patent Document 6), an agent containing astaxanthin and/or an ester thereof (for example, Patent Document 7), and an agent containing both an Apocynum venetum L. extract and a vitamin C compound (for example, Patent Document 8).
Further, Patent Document 9 discloses an application, as an agent for preventing and treating hyperlipemia, of γ-orizanol, which is a mixture of compounds obtained by independently binding campesterol, β-sitosterol, cycloartenol, 24-methylene cycloartanol, and cyclobranol to ferulic acid ester. Patent Document 10 discloses that single administration of any one of cycloartenol and 24-methylcycloartenol leads to a decrease in cholesterol in blood plasma and a decrease in high-density lipoprotein cholesterol (HDL-C) and leads to no significant change in TG, PL, and LPO.
Moreover, antioxidants such as 3,5-tert-butyl-4-hydroxytoluene (BHT) and 2,3-tert-butyl-hydroxyanisole (BHA) have been developed to inhibit oxidation of a lipid or the like. However, such antioxidants may be carcinogens (for example, Non Patent Document 3) and are difficult to use safely.
Under such circumstances, development of a novel antioxidative substance which can be used safely and has no side effects has been desired.
Note that, an agent for improving hyperglycemia, an agent for improving pancreatic function, an agent for improving insulin resistance, and an agent for inhibiting visceral fat accumulation, each of which contains a cyclolanostane compound such as 9,19-cyclolanostane-3-ol or 24-methylene-9,19-cyclolanostane-3-ol, or a lophenol compound such as methylcholest-7-en-3-ol, 4-methylergost-7-en-3-ol, or 4-methylstigmast-7-en-3-ol as an active ingredient, are known (as in Patent Documents 11 to 13, Patent Documents 14 and 15, Patent Documents 16 and 17, and Patent Document 18, respectively).